Elizabeth I. Opara

Correlation between food intake and CSF IL-1 alpha in anorectic tumor bearing rats

Postulating that central IL-1 is involved in the pathogenesis of cancer anorexia we measured IL-1 alpha in cerebrospinal fluid (CSF) from anorectic tumor bearing (TB) rats and non-tumor bearing controls, and correlated their CSF IL-1 alpha with food intake and tumor weight. Food intake in controls was significantly higher than that in anorectic TB rats. Eight of the 13 anorectic TB rats had detectable CSF IL-1 alpha; no CSF IL-1 alpha was detected in controls. In anorectic TB rats a negative correlation existed between CSF IL-1 alpha and food intake and a positive correlation between CSF IL-1 alpha and tumor weight. Data suggest a link between CSF IL-1 alpha and the pathogenesis of cancer anorexia.

Culinary herbs and spices: their bioactive properties, the contribution of polyphenols and the challenges in deducing their true health benefits

Herbs and spices have been used for both culinary and medicinal purposes for centuries. Over the last decade, research into their role as contributors of dietary polyphenols, known to possess a number of properties associated with reducing the risk of developing chronic non-communicable diseases, has increased. However, bearing in mind how these foods are consumed, normally in small quantities and in combination with other foods, it is unclear what their true benefit is from a health perspective. The aim of this review is to use the literature to discuss how preparative and digestive processes, bioavailability and interactions between foods may influence the bioactive properties of these foods, and whether or not polyphenols are responsible for these properties. Furthermore, this review aims to highlight the challenges that need to be addressed so as to determine the true benefits of these foods and the mechanisms of action that underpin their purported efficacy.

An Investigation of the Relationship between the Anti-Inflammatory Activity, Polyphenolic Content, and Antioxidant Activities of Cooked and In Vitro Digested Culinary Herbs

There is little research on how cooking and digestion affect the anti-inflammatory activity of culinary herbs. Thus, the aim of this paper was to investigate this activity following cooking and in vitro digestion of the common culinary herbs, rosemary, sage, and thyme, and the relationship between their anti-inflammatory activity, polyphenol content, and antioxidant capacity. The anti-inflammatory activity of uncooked (U), cooked (C), cooked and in vitro digested (C&D), and standardised (STD, 30 mg/mL) culinary herbs was assessed by measuring their effect on interleukin 8 (IL-8) release from stimulated human peripheral blood lymphocytes (PBLs) and Caco-2 cells. The trolox equivalent capacity (TEAC) and estimated total phenolic content of the herbs were also determined. There was a significant decrease in IL-8 release from PBLs stimulated with H2O2 incubated with (U), (C), (C&D), and (STD) herbs and from Caco-2 cells stimulated with TNFα incubated with (C&D) and (STD) herbs. PBLs pre-incubated with (C&D) herbs prior to stimulation (H2O2 or TNFα) caused a significant inhibition in IL-8 release. The significant correlations between TEAC and estimated phenolic content and the anti-inflammatory activity suggest a possible contributory role of polyphenols to the anti-inflammatory activity of the culinary herbs investigated.

Mode of food intake reduction in Lewis rats with indomethacin-induced ulcerative ileitis

The mechanism of anorexia in inflammatory bowel disease is poorly understood. To gain insight into possible pathophysiologic mechanisms, the feeding indices and food intake were studied in an animal model of Crohns disease. The anorexia of indomethacin-induced ulcerative ileitis was compared with that of the well-known anorexia of total parenteral nutrition (TPN). Forty-five female Lewis rats were randomized to four groups: Control, Indomethacin, Indomethacin + TPN, and TPN. Feeding indices and food intake were continuously measured using the Automated Computerized Rat Eater Meter. Interleukin-1 alpha (IL-1 alpha), tumor necrosis factor-alpha (TNF-alpha), prostaglandin E2 (PGE2), and leukotriene B4 (LTB4) were assayed in plasma, mononuclear cell culture, or ileum to determine their role in mediating anorexia. In the TPN group, spontaneous food intake (SFI) decreased (52%; p < 0.05), primarily via reduction in meal number (MN, 54%; p < 0.05) and, to a lesser extent, meal size (MZ, 35%; p < 0.05). In comparison, in the Indomethacin group SFI decreased (74%; p < 0.05) primarily via reduction in MZ (67%, p < 0.05); MN also decreased but to a lesser extent (27%; p < 0.05). In the Indomethacin + TPN group, SFI decreased (55%; p > 0.05) primarily via reduction in MN (79%; p < 0.05), whereas MZ decreased slightly (19%; p < 0.05). Only in the Indomethacin group were IL-1 alpha and TNF-alpha detected in the mononuclear cell culture and plasma, respectively. In the Indomethacin group, an inverse correlation existed between MZ and TNF-alpha (p < 0.05). In the Indomethacin group, IL-1 alpha, PGE2, and LTB4 concentrations did not correlate with feeding indices. SFI reduction in this model was mediated primarily via a decrease in MZ. TNF-alpha is proposed to mediate this effect and TPN was shown to overcome the effect on MZ.

The efficacy and safety of Chinese herbal medicines

The uses and practice of traditional Chinese medicines (TCM) date back centuries and are steeped in customs that encompass ancestral beliefs (concerning health), drug lore and “an understanding of natural laws” (Hesketh & Zhu, 1997; Unschuld, 1999). Today TCM (on its own or in conjunction with conventional medicine) is an integral component of healthcare systems in the Far East and is used to treat disease and to promote health and wellbeing (Hesketh & Zhu, 1997; Scheid, 2000; Bodeker, 2001; Wang & Ren, 2002). Over the past decade, Western medicine has witnessed the keen embracing of certain elements of TCM, especially Chinese herbal medicines (CHM) and their commercial derivatives. These medicines are said to possess numerous properties and as a consequence are used to treat a variety of diseases including arthritis, cancer, asthma and allergies (Brooks & Lowenthal, 1977; But & Chang, 1996; Chan & Critchley, 1996). Ganoderma lucidum, or ‘Lingzhi’, the focus of the paper by Wachtel-Galor et al. (2004b) in this issue of the British Journal of Nutrition is a prime example of the multifarious nature of CHM. G. lucidum is a very popular Chinese medicinal fungus, which has long been used as a sedative. It is reported to possess anti-tumour, anti-hepatotoxic, antinociceptive and immunomodulatory properties and has been used in the treatment of hypercholesterolaemia and hypertension (Jong & Birmingham, 1992; Lin et al. 1995; Koyama et al. 1997; Wang et al. 1997, 2002; Wasser & Weis, 1999; Bao et al. 2001a,b; Liu et al. 2002). Moreover, the immunomodulatory properties of G. lucidum have been exploited in the development of possible treatments for both allergic asthma and food allergy (Li et al. 2000, 2001). G. lucidum is also used as a dietary supplement and health food (Chiu et al. 2000). With the increasing use of CHM, such as G. lucidum, come the questions concerning their safety, regulation, efficacy and mode of action (Chan et al. 1993; Chan & Critchley, 1996; Tang et al. 1999; Ernst, 2000, 2003; Fugh-Berman, 2000; Mills, 2001). The use of CHM has been connected to a number of adverse effects resulting in nephropathy, acute hepatitis, coma and fever. In addition, neurological, cardiovascular and gastrointestinal problems have also been associated with CHM (Chan et al. 1993; Vanherweghem et al. 1993; Chan & Critchley, 1996; Lord et al. 1999; Nortier et al. 2000; Park et al. 2001). Cases of poisoning have been linked to variations in the chemical composition of different brands of the same herb. Such differences may arise as a result of inadequate processing (processing normally involves soaking and boiling the raw material) resulting in toxins being retained, and adulteration with cheaper substitutes (Chan & Critchley, 1996; Fugh-Berman, 2000; Li & Sampson, 2003). (Adulteration may also obscure the true benefits of CHM as well as contribute to them (Keane et al. 1999).) Cases of poisoning may also be attributed to heavy metals (Cd, Pb, Tl and Hg) present in both unprocessed CHM and their commercial derivatives (Wong et al. 1993; Chan & Critchley, 1996; Chiu et al. 2000). The misclassification of species and the mistaken substitution of Chinese herbs have also given rise to serious adverse affects (Chan et al. 1993; Vanherweghem et al. 1993; But, 1994; Chan & Critchley, 1996; Fugh-Berman, 2000). For example, a product believed to contain ‘Siberian ginseng’ but on analysis was shown to contain Chinese Silk Vine, has been linked to a case of neonatal androgenisation in North America (Koren et al. 1990; Awang, 1991). Misidentification of CHM can also lead to erroneous explanations concerning their mode of action. In correspondence concerning the anti-allergic properties of the CHM ‘Food Allergy Herbal Formula-1’ (FAHF-1), the incorrect identification of the chemical structure of one of its components (G. lucidum) led to ‘misleading conclusions’ about the causes of FAHF-1’s immunomodulatory action (Li et al. 2001; Claman, 2002; Towers, 2003; Li & Sampson, 2003). Concerns about CHM have been further reinforced by the potential for their interactions with conventional medicines causing effects that may ultimately result in modifications to the action(s) of the conventional medicines (Chan & Critchley, 1996; Chen et al. 2002; Fugh-Berman, 2000). An example of such an interaction is that of warfarin and Angelica sinensis (dong quai) or Salvia miltiorrhiza (danshen). Evidence suggests that the bioavailability and elimination rate of warfarin, plus platelet function, are affected by these CHM (Chan & Critchley, 1996; Fugh-Berman, 2000). Clearly these issues highlight the need for further in-depth research on CHM and other herbal medicines. The National Center for Complementary and Alternative Medicine (NCCAM; http://nccam.nih.gov), a US Congress-funded body, actively supports research and development in the area of CHM. In addition, the Department of Complementary Therapies at Exeter University in the UK has highlighted the need to adhere to rigorous scientific methodology in the carrying out of research on CHM and other alternative and complementary therapies (www.ex.ac.uk/FACT). In studies on CHM, a variety of approaches have been used. Some studies have focused on analysis, others on biological activities, safety, bioavailability and mode of action using either cell or animal models (Lin et al. 1995; Kawagishi et al. 1997; Chiu et al. 2000; Bao et al. 2001a,b; Chen et al. 2002; Wang et al. 2002; Xu et al. 2003). Many studies have used randomised controlled trials (RCT) to address the question of efficacy. A systematic British Journal of Nutrition (2004), 91, 171–173 DOI: 10.1079/BJN20031060 q The Author 2004

Studies on the regulation of food intake using rat total parenteral nutrition as a model

Total parenteral nutrition (TPN) is essential for maintaining the nutritional status of patients who are unable to eat sufficiently to meet their metabolic needs. However, TPN suppresses appetite and ultimately diminishes food intake. Theories concerning the role(s) of peripheral metabolites as signals, acting via the liver and the hypothalamus, for the metabolic control of food intake, have been put forward to explain the anorectic effect of TPN. In addition, it is postulated that changes in peripheral metabolites during TPN may be translated into changes in the levels of brain neurotransmitters known to decrease food intake. This review summarizes studies concerning the effect of TPN on food intake. These studies have involved: (1) characterizing the changes in feeding activity due to TPN; (2) investigating the involvement of the central nervous system; and (3) investigating the role of the periphery and its metabolites in the regulation of food intake during TPN. Some insight into the mechanism of action of TPN on food intake is provided.

Use of a flow cell bioreactor as a chronic toxicity model system.

We describe the use of a model system to mimic chronic toxin exposure, similar to that which might be found in a human situation, where exposure to dietary or environmental toxins occurs at a low level for an extended period of time. This is in contrast to the acute, immediately toxic dose effect usually observed in flask tissue culture. The apparatus used was a flow cell bioreactor in which cells can be cultured for lengthy periods of time as a continuous viable population. The compound used as the toxic agent was 3-nitropropanoic acid (3-NPA), a fungal neurotoxin which acts as a suicide inhibitor of succinate dehydrogenase. The secondary human cell line, Int 407, was tested in conventional flask culture for periods of up to 72 hours to determine the no-observed-effect level (NOEL) for 3-NPA. Cell populations established in the bioreactor were continuously exposed to levels of 3-NPA below that of the NOEL for periods of up to 4 weeks and the viability of the population determined using MTT, trypan blue and ATP assays.

Immunoglobulin E mediated food allergy.Modelling and application of diagnostic and predictive tests for existing and novel foods

It is known that some foods cause an allergenic response in certain individuals. Clinical and immunological tests are available for the diagnosis of food allergy and identification of food allergens. However, there are no valid tests for the prediction of the allergenic potential of foods not normally recognized as allergenic. Such foods include: food products developed from foods which may not be recognizable as allergenic in their modified forms; foods produced using novel processes (novel foods), for example genetically modified foods; and foods not normally consumed but that are being used increasingly as alternatives to more traditional foods. Both the risks associated with food allergy and the fact that foods such as the ones described above will become available to the consumer, highlight the need for methods to screen for potential food allergens. This review provides a general overview of food allergy including mechanism, development and prevalence, but focuses on and discusses: 1) the possible risks (with specific reference to food allergy) associated with new and novel foods; and 2) the development/use of food allergy models (in vivo and in vitro) to assess the allergenic potential of new and novel foods.It is known that some foods cause an allergenic response in certain individuals. Clinical and immunological tests are available for the diagnosis of food allergy and identification of food allergens. However, there are no valid tests for the prediction of the allergenic potential of foods not normally recognized as allergenic. Such foods include: food products developed from foods which may not be recognizable as allergenic in their modified forms; foods produced using novel processes (novel foods), for example genetically modified foods; and foods not normally consumed but that are being used increasingly as alternatives to more traditional foods. Both the risks associated with food allergy and the fact that foods such as the ones described above will become available to the consumer, highlight the need for methods to screen for potential food allergens. This review provides a general overview of food allergy including mechanism, development and prevalence, but focuses on and discusses: 1) the possible risks (with specific reference to food allergy) associated with new and novel foods; and 2) the development/use of food allergy models (in vivo and in vitro) to assess the allergenic potential of new and novel foods.

An in vitro based investigation of the cytotoxic effect of water extracts of the Chinese herbal remedy LD on cancer cells

BackgroundLong Dan Xie Gan Wan (LD), a Chinese herbal remedy formulation, is traditionally used to treat a range of conditions, including gall bladder diseases, hepatitis, hyperthyroidism, migraines but it is not used for the management or treatment of cancer. However some of its herbal constituents, specifically Radix bupleuri, Radix scutellariae and Rhizoma alismatis have been shown to inhibit the growth of cancer cells. Thus, the aim of the study was to investigate the impact of LD on cancer cells in vitro.MethodsHL60 and HT29 cancer cell lines were exposed to water extracts of LD (1:10, 1:50, 1:100 and/or 1:1000 prepared from a 3 mg/30 ml stock) and for both cell lines growth, apoptotic induction, alterations in cell cycle characteristics and genotoxicity were investigated. The specificity of the action of LD on these cancer cell lines was also investigated by determining its effect on human peripheral blood lymphocytes. Preliminary chemical analysis was carried out to identify cytotoxic constituents of LD using HPLC and LCMS.ResultsLD was significantly cytotoxic to, and induced apoptosis in, both cell lines. Apoptotic induction appeared to be cell cycle independent at all concentrations of LD used (1:10, 1:50 and 1:100) for the HL60 cell lines and at 1:10 for the HT29 cell line. At 1:50 and 1:100 apoptotic induction by LD appeared to be cell cycle dependent. LD caused significant genotoxic damage to both cell lines compared to their respective controls. The specificity study showed that LD exerted a moderate cytotoxic action against non-proliferating and proliferating blood lymphocytes but not apoptosis. Chemical analysis showed that a number of fractions were found to exert a significant growth inhibitory effect. However, the molecular weights of compounds within these fractions did not correspond to those from the herbal constituents of LD.ConclusionIt is possible that LD may have some chemotherapeutic potential. However, further studies are required to determine its cytotoxic constituents.

Determination of superoxide dismutase mimetic activity in common culinary herbs

BackgroundUnder conditions of oxidative stress, the removal of superoxide, a free radical associated with chronic inflammation, is catalysed by superoxide dismutase (SOD). Thus in addition to acting as an antioxidant, SOD may also be utilized as an anti-inflammatory agent. Some plant derived foods have been shown to have SOD mimetic (SODm) activity however it is not known if this activity is possessed by culinary herbs which have previously been shown to possess both antioxidant and anti-inflammatory properties. The aim of the study was to ascertain if the culinary herbs rosemary, sage and thyme possess SODm activity, and to investigate the influence of cooking and digestion on this activity. Transition metal ion content was also determined to establish if it could likely contribute to any SODm activity detected.FindingsAll extracts of uncooked (U), cooked (C) and cooked and digested (C&D) herbs were shown to possess SODm activity, which was significantly correlated with previously determined antioxidant and anti-inflammatory activities of these herbs. SODm activity was significantly increased following (C) and (C&D) for rosemary and sage only. The impact of (C) and (C&D) on the SODm for thyme may have been influenced by its transition metal ion content.ConclusionsSODm activity may contribute to the herbs’ antioxidant and anti-inflammatory activities however the source and significance of this activity need to be established.